This invention is in the field of medical procedures, namely laser medical equipment used in the delivery of anesthetics or pharmaceuticals to, or the removal of fluids, gases or other biomolecules from, a patient.
The traditional method for the collection of small quantities of fluids, gases or other biomolecules from a patient utilizes mechanical perforation of the skin with a sharp device such as a metal lancet or needle. Additionally, the typical method of administering anesthetics or other pharmaceuticals is through the use of a needle.
These procedures have many drawbacks, including the possible infection of health care workers and the public by the sharp device used to perforate the skin, as well as the cost of handling and disposal of biologically hazardous waste.
When skin is perforated with a sharp device such as a metal lancet or needle, biological waste is created in the form of the xe2x80x9csharpxe2x80x9d contaminated by the patient""s blood and/or tissue. If the patient is infected with blood-born agents, such as human immunodeficiency virus (HIV), hepatitis virus, or the etiological agent of any other diseases, the contaminated sharp poses a serious threat to others that might come in contact with it. For example, many medical workers have contracted HIV as a result of accidental contact with a contaminated sharp.
Post-use disposal of contaminated sharps imposes both logistical and financial burdens on the end user. These costs are imposed as a result of the social consequences of improper disposal. For example, in the 1980""s improperly disposed biological wastes washed up on public beaches on numerous occasions. Improper disposal also permits others, such as intravenous drug users, to obtain contaminated needles and spread disease.
There exists an additional drawback of the traditional method of using a needle for administering anesthetics or pharmaceuticals, as well as for drawing fluids, gases or other biomolecules. The pain associated with being stabbed by a the sharp instrument can be a traumatizing procedure, especially in pediatric patients, causing significant stress and anxiety in the patient. Moreover, for drawing fluids, gases or other biomolecules the stabbing procedure often must be repeated before sufficient fluid is obtained.
The current technology for applying local anesthetic without the use of needles typically involves either (a) topical lidocaine mixtures, (b) iontophoresis, (c) carriers or vehicles which are compounds that modify the chemical properties of either the stratum corneum, or the pharmaceutical, and (d) sonophoresis which involves modifying the barrier function of stratum corneum by ultrasound. A cream containing lidocaine is commonly used, especially in pediatric patients, but needs to be applied for up to 60 minutes, and anesthesia is produced to a depth of only about 4 mm. The lack of lidocaine penetration is a consequence of the barrier function of the stratum corneum. Inherent problems with iontophoresis include the complexity of the delivery system, cost, and unknown toxicology of prolonged exposure to electrical current. Additionally, the use of carriers or vehicles involves additional compounds which might modify the pharmacokinetics of the pharmaceutical of interest or are irritating.
Thus, a need exists for a technique to remove fluids, gases or other biomolecules or to administer anesthetics or other pharmaceuticals which does not require a sharp instrument. The method and apparatus disclosed herein fulfill this need and obviate the need for the disposal of contaminated instruments, thereby reducing the risk of infection.
Lasers have been used in recent years as a very efficient precise tool in a variety of surgical procedures. Among potentially new sources of laser radiation, the rare-earth elements are of major interest for medicine. One of the most promising of these is a YAG (yttrium, aluminum, garnet) crystal doped with erbium (Er) ions. With the use of this crystal, it is possible to build an erbium-YAG (Er:YAG) laser which can be configured to emit electromagnetic energy at a wavelength (2.94 microns) which is strongly absorbed by, among other things, water. When tissue, which consists mostly of water, is irradiated with radiation at or near this wavelength, energy is transferred to the tissue. If the intensity of the radiation is sufficient, rapid heating can result followed by vaporization of tissue. In addition, deposition of this energy can result in photomechanical disruption of tissue. Some medical uses of Er:YAG lasers have been described in the health-care disciplines of dentistry, gynecology and ophthalmology. See, e.g., Bogdasarov, B. V., et al., xe2x80x9cThe Effect of Er:YAG Laser Radiation on Solid and Soft Tissues,xe2x80x9d Preprint 266, Institute of General Physics, Moscow, 1987; Bol""shakov, E. N. et al., xe2x80x9cExperimental Grounds for Er:YAG Laser Application to Dentistry,xe2x80x9d SPIE 1353:160-169, Lasers and Medicine (1989) (these and all other references cited herein are expressly incorporated by reference as if fully set forth in their entirety herein).
The present invention employs a laser to perforate or alter the skin of a patient so as to remove fluids, gases or other biomolecules or to administer anesthetics or other pharmaceuticals. Perforation or alteration is produced by irradiating the surface of the target tissue with a pulse or pulses of electromagnetic energy from a laser. Prior to treatment, the care giver properly selects the wavelength, energy fluence (energy of the pulse divided by the area irradiated), pulse temporal width and irradiation spot size so as to precisely perforate or alter the target tissue to a select depth and eliminate undesired damage to healthy proximal tissue.
According to one embodiment of the present invention, a laser emits a pulsed laser beam, focused to a small spot for the purpose of perforating or altering the target tissue. By adjusting the output of the laser, the laser operator can control the depth, width and length of the perforation or alteration as needed.
In another embodiment continuous-wave or diode lasers may be used to duplicate the effect of a pulsed laser beam. These lasers are modulated by gating their output, or, in the case of a diode laser, by fluctuating the laser excitation current in a diode laser. The overall effect is to achieve brief irradiation, or a series of brief irradiations, that produce the same tissue permeating effect as a pulsed laser. The term xe2x80x9cmodulated laserxe2x80x9d is used herein to indicate this duplication of a pulsed laser beam.
The term, xe2x80x9cperforationxe2x80x9d is used herein to indicate the ablation of the stratum corneum to reduce or eliminate its barrier function. The term, xe2x80x9calterationxe2x80x9d of the stratum corneum is used herein to indicate a change in the stratum corneum which reduces or eliminates the barrier function of the stratum corneum and increases permeability without ablating, or by merely partially ablating, the stratum corneum itself. A pulse or pulses of infrared laser radiation at a subablative energy of, e.g., 60 mJ (using a TRANSMEDICA(trademark) International, Inc. (xe2x80x9cTRANSMEDICA(trademark)xe2x80x9d) Er:YAG laser with a beam of radiant energy with a wavelength of 2.94 microns, a 200 xcexcs (microsecond) pulse, and a 2 mm spot size) will alter the stratum corneum. The technique may be used for transdermal drug delivery or for obtaining samples, fluids, gases or other biomolecules, from the body. Different wavelengths of laser radiation and energy levels less than or greater than 60 mJ may also produce the enhanced permeability effects without ablating the skin.
The mechanism for this alteration of the stratum corneum is not certain. It may involve changes in lipid or protein nature or function or be due to desiccation of the skin or mechanical alterations secondary to propagating pressure waves or cavitation bubbles. The pathway that topically applied drugs take through the stratum corneum is generally thought to be through cells and/or around them, as well as through hair follicles. The impermeability of skin to topically applied drugs is dependent on tight cell to cell junctions, as well as the biomolecular makeup of the cell membranes and the intercellular milieu. Any changes to either the molecules that make up the cell membranes or intercellular milieu, or changes to the mechanical structural integrity of the stratum corneum and/or hair follicles can result in reduced barrier function. It is believed that irradiation of the skin with radiant energy produced by the Er:YAG laser causes measurable changes in the thermal properties, as evidenced by changes in the Differential Scanning Calorimeter (DSC) spectra as well as the Fourier Transform Infrared (FTIR) spectra of the stratum corneum. Changes in DSC and FTIR spectra occur as a consequence of changes in molecules or macromolecular structure, or the environment around these molecules or structures. Without wishing to be bound to any particular theory, we can tentatively attribute these observations to changes in lipids, water and protein molecules in the stratum corneum caused by irradiation of molecules with electromagnetic radiation, both by directly changing molecules as well as by the production of heat and pressure waves which can also change molecules.
Both perforation and alteration change the permeability parameters of the skin in a manner which allows for increased passage of pharmaceuticals, as well as fluids, gases or other biomolecules, across the stratum corneum.
Accordingly, one object of the present invention is to provide a means for perforating or altering the stratum corneum of a patient in a manner that does not result in bleeding. For example, the perforation or alteration created at the target tissue is accomplished by applying a laser beam that penetrates through the stratum corneum layer or both the stratum corneum layer and the epidermis, thereby reducing or eliminating the barrier function of the stratum corneum. This procedure allows the administration of anesthetics or other pharmaceuticals, as well as the removal of fluids, gases or other biomolecules, through the skin. Moreover, this procedure allows drugs to be administered continually on an outpatient basis over long periods of time. The speed and/or efficiency of drug delivery is thereby enhanced for drugs which were either slow or unable to penetrate skin.
In another embodiment of this invention, pressure waves, plasma, and cavitation bubbles are created in or above the stratum corneum to increase the permeation of the compounds (e.g., pharmaceuticals) or fluid, gas or other biomolecule removal. This method may simply overcome the barrier function of intact stratum corneum without significant alteration or may be used to increase permeation or collection in ablated or altered stratum corneum. As described herein, pressure waves, plasma, and cavitation bubbles are produced by irradiating the surface of the target tissue, or material on the target tissue, with a pulse or pulses of electromagnetic energy from a laser. Prior to treatment, the care giver properly selects the wavelength, energy fluence (energy of the pulse divided by the area irradiated), pulse temporal width and irradiation spot size to create the pressure waves, plasma, or cavitation bubbles while limiting undesired damage to healthy proximal tissue.
A further object of this invention is to provide an alternative means for administering drugs that would otherwise be required to be taken through other means, such as orally or injected, thereby increasing patient compliance and decreasing patient discomfort.
An additional object of this invention is to allow the taking of measurements of various fluid constituents, such as glucose, or to conduct measurements of gases.
A further object of this invention is to avoid the use of sharps. The absence of a contaminated sharp will eliminate the risk of accidental injury and its attendant risks to health care workers, patients, and others that may come into contact with the sharp. The absence of a sharp in turn obviates the need for disposal of biologically hazardous waste. Thus, the present invention provides an ecologically sound method for administering anesthetics or other pharmaceuticals, as well as removing fluids, gases or other biomolecules.
In another embodiment a typical laser is modified to include a container unit. Such a container unit can be added to: (1) increase the efficiency in the collection of fluids, gases or other biomolecules; (2) reduce the noise created when the laser beam perforates the patient""s tissue; and (3) collect the ablated tissue. The optional container unit is alternatively evacuated to expedite the collection of the released materials such as the fluids, gases or other biomolecules. The container can also be used to collect only ablated tissue. The noise created from the laser beam""s interaction with the patient""s skin may cause the patient anxiety. The optional container unit reduces the noise intensity and therefore alleviates the patient""s anxiety and stress. The container unit also minimizes the risk of cross-contamination and guarantees the sterility of the collected sample. The placement of the container unit in the use of this invention is unique in that it covers the tissue being irradiated, at the time of irradiation by the laser beam, and is therefore able to collect the fluid, gas or other biomolecule samples and/or ablated tissue as the perforation or alteration occurs. The container unit may also be modified for the purpose of containing materials, such as drugs, which may be applied before, simultaneously or shortly after irradiation.
A typical laser used for this invention requires no special skills to use. It can be small, light-weight and can be used with regular or rechargeable batteries. The greater the laser""s portability and ease of use, the greater the utility of this invention in a variety of settings, such as a hospital room, clinic, or home.
Safety features can be incorporated into the laser that require that no special safety eyewear be worn by the operator of the laser, the patient, or anyone else in the vicinity of the laser when it is being used.